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Article Publish Status: FREE
Abstract Title:

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.

Abstract Source:

PLoS One. 2018 ;13(1):e0191934. Epub 2018 Jan 31. PMID: 29385186

Abstract Author(s):

Soria Eladak, Delphine Moison, Marie-Justine Guerquin, Gabriele Matilionyte, Karen Kilcoyne, Thierry N'Tumba-Byn, Sébastien Messiaen, Yoann Deceuninck, Stéphanie Pozzi-Gaudin, Alexandra Benachi, Gabriel Livera, Jean-Philippe Antignac, Rod Mitchell, Virginie Rouiller-Fabre, René Habert

Article Affiliation:

Soria Eladak

Abstract:

BACKGROUND: Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.

METHODS: Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.

RESULTS: With first trimester human testes, using the hFeTA model, 10μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial markerMAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.

CONCLUSIONS: Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Study Type : Human In Vitro

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